Low-Dose Aspirin for Individualized Cancer Prevention in Older Adults: A Secondary Analysis of the ASPREE Randomized Clinical Trial.

Identifying individuals likely to experience benefit or harm is crucial for guiding personalized prevention strategies.

确定可能受益或受损的个体对于指导个性化预防策略至关重要。

Background

To identify subgroups of the older population who may benefit most from LDA for cancer prevention by developing and validating an effect score model, including individual characteristics such as clonal hematopoiesis of indeterminate potential (CHIP) and other factors, to predict the individualized treatment effects (ITEs) of LDA in cancer incidence.

为了识别可能从低剂量阿司匹林（LDA）癌症预防中受益最多的老年人亚组，我们开发并验证了一个效应评分模型，包括克隆性造血潜能不确定（CHIP）等个体特征和其他因素，以预测LDA在癌症发生率上的个体化治疗效果（ITEs）。

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study is a nonprespecified secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial conducted between 2010 and 2014.

设计、设置和参与者：这是一项比较有效性研究，是对2010年至2014年间进行的老年人阿司匹林减少事件（ASPREE）随机临床试验的非预定次要分析。

Australian community-dwelling ASPREE participants (aged ≥70 years) provided biospecimen samples for CHIP testing.

澳大利亚社区居住的ASPREE参与者（年龄≥70岁）提供了生物样本用于CHIP检测。

CHIP was measured in 18 genes using a targeted sequencing assay.

使用靶向测序检测法在18个基因中测量CHIP。

Analyses were conducted between May 2023 and July 2025.

分析工作于2023年5月至2025年7月期间进行。

exposures

LDA (100 mg per day) or placebo.

给予LDA（每日100毫克）或安慰剂。

main_outcomes_and_measures

The primary outcome was overall cancer incidenceat 5 years.

主要结果是5年内的总体癌症发生率。

Twelve candidate models for predicting ITEs were assessed; the final model was selected to maximize cancer risk reduction and internally validated using bootstrapping.

评估了12个候选模型以预测个体治疗效果（ITEs）；最终模型被选用来最大化癌症风险降低，并使用自助法进行了内部验证。

Participants were grouped into treatment-favorable (ITE >0) and treatment-unfavorable (ITE <0) subgroups based on the final predictive model.

参与者根据最终预测模型被分为治疗有利（ITE>0）和治疗不利（ITE<0）亚组。

Results

A total of 9350 participants were included in the analysis (median age, 73.7 [IQR, 71.6-77.1] years; 5021 females [53.7%]) to LDA (4667 [49.9%]) or placebo (4683 [50.1%]).

分析共纳入9350名参与者（中位年龄73.7岁，四分位数间距71.6-77.1岁；5021名女性[53.7%]），分别接受LDA（4667名[49.9%]）或安慰剂（4683名[50.1%]）。

The median follow-up was 4.5 (IQR, 3.3-5.5) years.

中位随访时间为4.5年（四分位数间距，3.3-5.5年）。

Factors associated with LDA benefit included older age, nonsmoking status, CHIP with a variant allele frequency of 10% or greater, family history of cancer, and lower body mass index.

与低剂量阿司匹林（LDA）益处相关的因素包括年龄较大、非吸烟状态、具有10%或更高变异等位基因频率的克隆造血（CHIP）、癌症家族史以及较低的身体质量指数。

CHIP was the strongest predictor of benefit.

CHIP是获益最强的预测指标。

Personalized treatment based on the model improved 5-year absolute cancer risk reduction by a median of 2.3% (IQR, 0.7%-3.7%) compared with a treat-all approach (LDA to all participants).

基于该模型的个性化治疗与全面治疗相比，5年绝对癌症风险降低了中位数2.3%（四分位数间距，0.7%-3.7%）（对所有参与者进行LDA）。

LDA was associated with lower cancer risk (hazard ratio[HR], 0.85 [95% CI, 0.72-1.00]) in the treatment-favorable subgroup and higher cancer risk (HR, 1.14 [95% CI, 0.95-1.38]) in the treatment-unfavorable subgroup (P = .02 for heterogeneity).

LDA与较低的癌症风险相关（风险比[HR]，0.85 [95% 置信区间，0.72-1.00]）在治疗有利的亚组中，并且与较高的癌症风险相关（HR，1.14 [95% 置信区间，0.95-1.38]）在治疗不利的亚组中（异质性P = .02）。

conclusions_and_relevance

The findings of this study suggest significant heterogeneity in the effectiveness of LDA for cancer prevention among older adults, with CHIP identified as a key predictive factor.

本研究的结果表明，LDA在老年人癌症预防中的有效性存在显著异质性，其中CHIP被确定为一个关键的预测因素。

Further study is needed to fully understand the implications of these findings.

需要进一步研究以全面理解这些发现的含义。

trial_registration

ClinicalTrials.gov Identifier: NCT01038583.

ClinicalTrials.gov 注册号：NCT01038583。